In the open-label trial, 372 adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 sites in the U.S., Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the United Kingdom, Japan, and Australia were randomized between December 2012 and January 2016 to receive mogamulizumab 1.0 mg/kg intravenously (IV) weekly for the first 28-day cycle and then on days 1 and 15 of subsequent cycles (n = 186) or vorinostat 400 mg daily (n = 186). Treatment was continued until progression or unacceptable toxicity. Patients had to have failed at least one previous systemic therapy. Randomization was stratified by disease subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB–II vs III–IV).

The primary endpoint was progression-free survival on investigator assessment in the intention-to-treat population. Patients in the vorinostat group could cross over to mogamulizumab treatment upon progression or intolerable toxicity.

At data cutoff, 27 patients receiving mogamulizumab and 10 receiving vorinostat remained on study treatment; 31 patients in the vorinostat group who crossed over to mogamulizumab also remained on treatment. Median duration of follow-up was 17.0 months in the randomized phase of the study.

Overall response by global assessment occurred in 28% vs 5% of patients (P < .0001). A total of 136 vorinostat patients (73%) crossed over to mogamulizumab therapy (109 due to progression, 27 due to toxicity). Post-hoc analysis showed that median progression-free survival was 8.4 months among the 319 patients who were either randomized to or crossed over to mogamulizumab. An exploratory analysis of overall survival showed that median survival was not reached in the mogamulizumab group vs 43.9 months in the vorinostat group (HR = 0.93, P = .9439).

Adverse Events

The most common adverse events of any grade in the mogamulizumab group were infusion-related reactions (32% grade 1–2, 2% grade 3), drug rash (20% grade 1–2, 4% grade 3), diarrhea (23% grade 1–2, 1% grade 3), and fatigue (22% grade 1–2, 2% grade 3). Grade 3 or 4 adverse events occurred in 41% of the mogamulizumab group vs 41% of the vorinostat group, with the most common in the mogamulizumab group being pneumonia (5%), drug eruption (4%), and hypertension (4%) and the most common in the vorinostat group being thrombocytopenia (7%), fatigue (6%), and hypertension (6%). Serious adverse events occurred in 38% vs 25% of patients, with the most common in the mogamulizumab group being pyrexia (4%) and cellulitis (3%) and the most common in the vorinostat group being cellulitis (3%), pulmonary embolism (3%), and sepsis (3%). Adverse events led to discontinuation of treatment in 19% vs 23% of patients, with the most common causes being drug rash in the mogamulizumab group (7%) and fatigue in the vorinostat group (4%). Adverse events considered related to treatment resulted in death in two patients in the mogamulizumab group (due to sepsis and polymyositis) and three patients in the vorinostat group (two due to pulmonary embolism and one due to bronchopneumonia).

The investigators concluded, “Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma.”

The study was funded by Kyowa Kirin.

Youn H. Kim, MD, of the Departments of Dermatology and Medicine/Oncology, StanfordCancer Institute, Stanford University School of Medicine, is the corresponding author for The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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